The interactions between an autonomous parvovirus and cells of dissimilar differentiated phenotype are being studied in order to elucidate the mechanism behind the specific tissue-tropism exhibited by these teratogenic agents during pathogenesis. The small size of the viral genome, and therefore its limited coding potential, leads us to predict that the functions necessary for the successful replication of the virus are normal cellular functions which the virus has usurped for its own preferential use. Experimental infections of teratocarcinoma stem cells, and their differentiated derivatives have demonstrated that at least some of the host genes that the virus requires are developmentally controlled, and are expressed in only a small number of differentiated end-cells. Cell variants which are altered in their response to virus infection will be studied using the techniques of molecular biology and somatic cell genetics in an attempt to determine the number of these genes, the nature of their epigenetic control, their mode of action in virus replication and their function in normal uninfected cells. Virus mutants with different target cell specificities will be studied in order to identify the region within the viral genome which determines the differentiated cell type which the virus can lytically infect. By constructing novel host cells we will attempt to select or create new virus variants which will infect and kill specific tumor cell types and so generate tools for directed oncolysis in the whole animal.